Using heparin affinity chromatography, a novel fibroblast and vascular smooth muscle cell mitogen has been isolated from the conditioned medium of the human histiocytic lymphoma cell line U-937. Analysis of cDNA clones has shown that this factor is a new member of the EGF/TGFalpha family of proteins, and it has therefore provisionally been named heparin-binding EGF-like growth factor (HBEGF). Ample evidence has now accumulated indicating that various aspects of the process of wound repair can be accelerated by the application of particular growth factors. The long-term objectives of this project are therefore (i) to determine whether HBEGF is efficacious in accelerating normal and/or various types of impaired wound healing; and (ii) to determine whether HBEGF has in vivo activities that distinguish it therapeutically from other known growth factors. The principal goal of Phase I of the project is to generate reagents (HBEGF recombinantly produced mammalian cells; antibodies against HBEGF) to allow a more detailed study of the biology of this factor. In addition, an initial test of the wound healing activity of HBEGF will be conducted in a full-thickness wound model in impaired (diabetic, db/db) and normal (db/+m) mice.